Sars-Cov-2 Omicron (B11529) Variant Infection Leads to High Morbidity and Mortality in Unvaccinated Patients with Cancer

Background: The Omicron (B.1.1.529) SARS-CoV-2 variant is highly transmissible and escapes vaccinal immunity. Evidence is lacking as to the impact of Omicron in oncological patients. Method(s): Capitalizing on OnCovid study data (NCT04393974), we analysed COVID-19 morbidity and case fatality rate at 28 days (CFR28) of unvaccinated patients across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: "Pre-vaccination" phase (27/02/2020-30/11/2020), "Alpha- Delta variant" phase (01/12/2020-14/12/2021), "Omicron variant" phase (15/12/2021-31/01/2022). Finding(s): By the data lock of 04/02/2022, 3820 patients from 37 institutions across 6 countries were entered. Out of 3473 eligible patients, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. In total 659 (61.3%) and 42 (11.5%) were unvaccinated in the Alpha-Delta and Omicron. Unvaccinated patients across the Omicron, Alpha-Delta and Pre-vaccination phases experienced similar CFR28 (27.5%, 28%, 29%, respectively). Following propensity score matching, 42 unvaccinated Omicron patients were matched with 122 and 121 patients from the Pre-vaccination and Alpha-Delta phases respectively, based on country of origin, sex, age, comorbidity burden, primary tumour, cancer stage and status, and the receipt of systemic anticancer therapy at COVID-19. Unvaccinated Omicron patients experienced improved COVID-19 outcomes in comparison to patients diagnosed during the Prevaccination phase. Morbidity and mortality were comparable to those of unvaccinated patients diagnosed during the Alpha-Delta phase. Interpretation(s): Despite time-dependent improvements in outcomes reported in the Omicron phase, patients with cancer remain highly vulnerable to SARS-CoV-2 in absence of vaccinal protection. This study provides unequivocal evidence in support of universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.

Clinical effectiveness of SARS-CoV-2 vaccines and booster doses in patients with cancer: An analysis from the European OnCovid registry

Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR14) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts' characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.

Prevalence and impact of COVID-19 sequelae on treatment pathways and survival of cancer patients who recovered from SARS-Cov-2 infection

Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment.

Covid-19 analysis from the multicenter, prospective, observational invidia-2 study (Influenza Vaccine Indication During Therapy With Immune Checkpoint Inhibitors: A Transversal Challenge)-a ficog study

Background: The prospective, multicenter, observational INVIDIa-2 study was designed to investigate the clinical efficacy of influenza vaccination in advanced cancer patients receiving immune checkpoint inhibitors (ICIs) from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until April 30, 2020. All ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the INVIDIa-2 study prospectively recorded all the COVID-19 ILI events. Methods: Patients were included in this non-prespecified COVID-19 preliminary analysis if potentially exposed to Sars-Cov-2 infection, namely alive on January 31, 2020, when the Italian government declared the National emergency. The incidence of confirmed COVID-19 was assessed among patients with ILI symptoms, describing the hospitalization rate and mortality. Cases with clinicalradiological diagnosis of COVID-19 without laboratory confirmation (COVID-like ILIs), were also reported. The COVID-incidence was exploratively compared basing on influenza vaccination. Results: 1260 patients receiving ICI were enrolled between October 2019 and January 2020;955 patients were analyzed according to the inclusion criterion. Of them, 66 patients had ILI from January 31, to April 30, 2020. 9 were COVID-19 ILIs with laboratory test confirmation. The COVID-19 ILI incidence was 0.9% (9/955 cases), with hospitalization rate of 100% and mortality rate of 67%. Including 5 COVID-like ILIs, the overall COVID-19 incidence was 1.5% (14/955), with hospitalization in 100% of cases and mortality rate of 64%. COVID-19 incidence was 1.2% for patients vaccinated against influenza (6/482 cases) and 1.7%, among unvaccinated patients (8/473 including 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference was not statistically significant, and the clinical trend in favor of vaccinated patients was lost when considering only confirmed COVID-19 (1.2% in vaccinated vs 0.6% in unvaccinated patients, p = 0.33), probably due to the greater presence of male and elderly patients in the vaccinated group (p = 0.009). Conclusions: We obtained the first prospective epidemiological data about symptomatic COVID-19 in advanced cancer patients receiving ICIs. The overall symptomatic COVID-incidence is meaningful, requiring hospitalization in all cases and leading to a high mortality rate, likely due advanced cancer more than to ICI therapy [Mengyuan Dai, Cancer Discov 2020].

Influenza-like illness and SARS-Cov-2 in the multicenter, prospective, observational INVIDIa-2 study (INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: A transversal challenge): A FICOG study

Background: The susceptibility of advanced cancer patients treated with immune checkpoint inhibitors (ICI) for viral infections has not been investigated. Currently, there are no robust data supporting the efficacy, safety and recommendation for influenza vaccination in cancer patients receiving ICI. Methods: The prospective, multicenter, observational INVIDIa-2 study investigated the clinical efficacy of influenza vaccination in advanced cancer patients with solid tumors receiving ICI between October 2019 and January 2020. The incidence of influenza-like illness (ILI, primary endpoint) was observed until April 30, 2020. Secondary endpoints included a non-prespecified analysis for COVID-19. Results: The study enrolled 1279 patients;1188 were evaluable. Of them, 11 patients developed ILI symptoms with confirmed diagnosis of COVID-19 (incidence of 0.9% and lethality of 72%, irrespective of the flu vaccination). Of the remaining 1177 patients, 574 received flu vaccination (48.8%). The ILI incidence was 7.7% (91 patients of 1177). Patients receiving the flu vaccine were significantly more frequently elderly (p<0.0001), former or active smokers (p<0.0001), affected by lung cancer (p=0.017) and by non-cancer comorbidities (p<0.0001) when compared to unvaccinated patients. The flu vaccine did not prevent ILI in the study population, irrespective of the vaccine type (quadrivalent vs trivalent, adjuvated vs non): the incidence of ILI was 8.2% in vaccinated vs 7.3% in unvaccinated patients (p=0.57). ILI complications were significantly less frequent for patients receiving flu vaccine (12.8% vs 40.9%, p=0.002). Hospital admission due to ILI occurred for 10 patients (11% of ILI cases;7 were unvaccinated). The ILI lethality was 2.2% (2 of 91 patients, both unvaccinated). Among vaccinated patients, those receiving adjuvated vaccines had lower incidence of ILI (4.8% vs 9.9%, p=0.046). Conclusions: Flu vaccination was not effective for ILI prevention, nor for COVID-19. Nevertheless, it reduced ILI complications, with no ILI-related deaths in vaccinated patients. We recommend the vaccine in ICI-treated cancer patients. Clinical trial identification: Eudract number of the trial: 2020-002603-18. Legal entity responsible for the study: FICOG Federation of Italian Cooperative Oncology Groups. Funding: FICOG (Federation of Italian Cooperative Oncology Groups, promoter and main sponsor), in turn funded by Seqirus UK and Roche S.p.A. for the present study. Disclosure: M. Bersanelli: Research grant/Funding (self), Research grant/Funding (institution), for the present study: Seqirus and Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, for other activities outside the present study: Pfizer, BMS, Novartis. S. Buti: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb (BMS), Pfizer;MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. U. De Giorgi: Research grant/Funding (institution): AstraZeneca, Roche, Sanofi;Honoraria (self): Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi. P. Bonomo: Honoraria (self): Merck Serono, Angelini Pharma,. All other authors have declared no conflicts of interest.